Sun Yu, Li Huai, Yang Henry, Rao Mahendra S, Zhan Ming
Bioinformatics Unit, Research Resources Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Crit Rev Eukaryot Gene Expr. 2006;16(3):211-31. doi: 10.1615/critreveukargeneexpr.v16.i3.20.
Embryonic stem (ES) cells are pluripotent cells with indefinite replication potential and ability to differentiate into all types of cells. An understanding of the regulatory mechanisms responsible for pluripotency in ES cells is critical for realizing their potential in regenerative medicine and science. Cross-species studies on ES cells have identified pathways and networks that are either fundamental to or species-specific for self-renewal and differentiation. Although pluripotency as an essential function in multicellular organisms is conserved through evolution, mechanisms primed for differentiation contribute substantially to the differences among stem cells derived from different tissues or species. Transcriptome mapping analysis has determined the chromosomal domains of gene coexpression patterns specific to the ES state and demonstrated that regulation of ES cell development is operative at both the local chromosomal domain level and global level. Combinatorial signals from multiple pathways regulate the expression of key intrinsic factors critical for ES cell fate determination. The regulatory core formed by Oct4, Sox2, and Nanog, in particular, activates genes critical for self-renewal and represses genes initiating differentiation, controlling ES cell pluripotency. Here, we review recent findings on mechanisms controlling ES cell development. By integrating data from different sources, we present a global picture of how ES cells reach the decision of self-renewal or differentiation.
胚胎干细胞（ES细胞）是具有无限复制潜能且能分化为所有类型细胞的多能干细胞。了解ES细胞多能性的调控机制对于实现其在再生医学和科学中的潜力至关重要。对ES细胞的跨物种研究已经确定了对自我更新和分化至关重要或具有物种特异性的途径和网络。尽管多能性作为多细胞生物中的一项基本功能在进化过程中得以保留，但引发分化的机制在很大程度上导致了源自不同组织或物种的干细胞之间的差异。转录组图谱分析已经确定了ES细胞状态特有的基因共表达模式的染色体结构域，并表明ES细胞发育的调控在局部染色体结构域水平和全局水平上都起作用。来自多个途径的组合信号调节对ES细胞命运决定至关重要的关键内在因子的表达。特别是由Oct4、Sox2和Nanog形成的调控核心，激活对自我更新至关重要的基因，并抑制启动分化的基因，从而控制ES细胞的多能性。在此，我们综述了关于ES细胞发育调控机制的最新研究发现。通过整合来自不同来源的数据，我们呈现了ES细胞如何做出自我更新或分化决定的全局图景。
